文章：

用人巨细胞病毒感染星形胶质细胞移植小鼠建立胶质母细胞瘤模型

Generation of glioblastoma in mice engrafted with human cytomegalovirus-infected astrocytes 

原文发布日期：2024-03-29 

英文摘要：

Mounting evidence is identifying human cytomegalovirus (HCMV) as a potential oncogenic virus. HCMV has been detected in glioblastoma multiforme (GB). Herewith, we present the first experimental evidence for the generation of CMV-Elicited Glioblastoma Cells (CEGBCs) possessing glioblastoma-like traits that lead to the formation of glioblastoma in orthotopically xenografted mice. In addition to the already reported oncogenic HCMV-DB strain, we isolated three HCMV clinical strains from GB tissues that transformed HAs toward CEGBCs and generated spheroids from CEGBCs that resulted in the appearance of glioblastoma-like tumors in xenografted mice. These tumors were nestin-positive mostly in the invasive part surrounded by GFAP-positive reactive astrocytes. The glioblastoma immunohistochemistry phenotype was confirmed by EGFR and cMet gene amplification in the tumor parallel to the detection of HCMV IE and UL69 genes and proteins. Our results fit with an HCMV-induced glioblastoma model of oncogenesis in vivo which will open the door to new therapeutic approaches and assess the anti-HCMV treatment as well as immunotherapy in fighting GB which is characterized by poor prognosis. 

摘要翻译： 

越来越多的证据表明，人巨细胞病毒（HCMV）可能是一种致癌病毒。研究已在多形性胶质母细胞瘤（GB）中检测到HCMV存在。本研究首次通过实验证明：经CMV诱导产生的胶质母细胞瘤样细胞（CEGBCs）可在原位移植小鼠模型中形成胶质母细胞瘤。除已报道的致癌性HCMV-DB毒株外，我们还从GB组织中分离出三种HCMV临床毒株，这些毒株能将人类星形胶质细胞（HAs）转化为CEGBCs，并形成球状体，最终在被移植小鼠体内形成胶质母细胞瘤样肿瘤。这些肿瘤的侵袭区域主要呈现巢蛋白（nestin）阳性，周围被GFAP阳性反应性星形胶质细胞包围。通过检测肿瘤中EGFR和cMet基因扩增，同时检出HCMV IE及UL69基因和蛋白，进一步证实了该肿瘤的胶质母细胞瘤免疫组化表型。我们的研究结果验证了HCMV诱导的体内胶质母细胞瘤致癌模型，这将为开发新的治疗方法开辟道路，并有助于评估抗HCMV治疗及免疫疗法在对抗预后极差的胶质母细胞瘤中的应用价值。

原文链接：

Generation of glioblastoma in mice engrafted with human cytomegalovirus-infected astrocytes